Antiviral immunity is impaired in COPD patients with frequent exacerbations
File(s)
Published version
Author(s)
Singanayagam, Aran
Loo, Su-Ling
Calderazzo, Maria Adelaide
Finney, Lydia J
Trujillo Torralbo, Maria-Belen
Type
Journal Article
Abstract
Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro RV-infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate anti-microbial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.
Date Issued
2019-12
Date Acceptance
2019-09-08
Citation
American Journal of Physiology: Lung Cellular and Molecular Physiology, 2019, 317 (6), pp.L893-L903
ISSN
1040-0605
Publisher
American Physiological Society
Start Page
L893
End Page
L903
Journal / Book Title
American Journal of Physiology: Lung Cellular and Molecular Physiology
Volume
317
Issue
6
Copyright Statement
© 2019 the American Physiological Society. Licensed under Creative Commons Attribution CC-BY 4.0 ( https://creativecommons.org/licenses/by/4.0/deed.en_US ).
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Wellcome Trust
British Lung Foundation
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31513433
Grant Number
P33132
096382/Z/11/Z
PPRG15-9
Subjects
COPD
innate immunity
viral infection
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-12-06